Mavacamten: A Game Changer for Patients with HCM

Podcast Transcript

Announcer:

Welcome to Love Your Heart, brought to you by Cleveland Clinic's Sydell and Arnold Miller Family Heart, Vascular, and Thoracic Institute. These podcasts will help you learn more about your heart, thoracic, and vascular systems, ways to stay healthy, and information about diseases and treatment options. Enjoy.

Steven Nissen:

I'm Dr. Steve Nissen, and I'm here with Dr. Milind Desai, and we're going to talk about a new drug that's really an amazing breakthrough for patients called Mavacamten. So first of all, Dr. Desai.

Milind Desai:

Hello everybody, I'm Milind Desai. I'm the Director of the Hypertrophic Cardiomyopathy Center and Director of Clinical Operations at Cleveland Clinic in Cleveland, Ohio. And thank you for joining this podcast. Yes, Dr. Nissen, we have some exciting new developments in the field of hypertrophic cardiomyopathy. Specifically, earlier in 2022 around April or so, the FDA approved Mavacamten, which is a first in class cardiac myosin inhibitor, specifically developed to target hypertrophic cardiomyopathy. The things that are bad with HCM are very nicely targeted by this drug. It is now commercially approved and known as Camzyos in the market.

Steven Nissen:

So this is a really a breakthrough. There have been use of old drugs to treat the disorder, but as I understand it, they haven't worked all that well, at least not for everybody.

Milind Desai:

Yes. So this disease, we've known about it for almost 60 plus years, and there have been tremendous evolutions that have happened in its diagnosis management. But the treatment, what we use traditionally for this, the standard medical therapy included beta blockers, calcium channel blockers like verapamil and disopyramide. None of these were specifically developed for this disease process. Each one, people serendipitously figured out that it may work in HCM. Importantly, none of these drugs were developed and tested rigorously in what we call a randomized control trial, a clinical trial where we recruit patients, compare the drug to placebo to see if these help. So Mavacamten or Camzyos is essentially the first ever drug tested against placebo prospectively in patients with hypertrophic obstructive cardiomyopathy.

Steven Nissen:

Now, the other treatment, of course, for this disorder is surgery, where the thick muscle that causes the obstruction, the problem is shaved away. People are still undergoing surgery, but does Mavacamten provide an alternative?

Milind Desai:

Yes, so that's very important that you talked about it. Septal reduction therapy, one aspect or of one way of doing it is surgical myectomy where we shave the muscle. The other aspect is alcohol septal ablation, where we squirt some alcohol to shrink the muscle. The concept is to reduce the thickness of the wall that i causing obstruction to the flow of blood. And this works well and it has served us really well, but it requires a highly experienced team, a highly experienced surgeon/interventional cardiologist. And if you don't have a good team, a highly experienced team, your outcomes can be very heterogeneous. There are not enough centers doing this high impact surgery in a high volume practice. So there is clearly an unmet need for specifically developed drug therapies. Mavacamten fits nicely into that role. In a recent VALOR study that we presented and published in April of 2022, we showed that in highly symptomatic obstructive hypertrophic cardiomyopathy patients who were referred for septal reduction therapy... So each and every one met criteria, they were referred for surgery.

When we randomized them to placebo versus Mavacamten, 82 percent of patients at 16 weeks no longer met criteria for surgery. In fact, at 16 weeks, every patient was offered surgery, but 95 percent of patients chose not to undergo surgery or alcohol septal ablation because they were feeling good. And the eligibility was also surrounded by significant symptom improvement, significant improvement in their quality of life, significant improvement in their outflow tract gradients, as well as biomarkers. So overall, great performance.

Steven Nissen:

This is a drug that should be used by experts, not by general practitioners. Is that a fair statement?

Milind Desai:

Yes, at this point. The way Mavacamten works is it reduces the excess contractility of the heart. Sometimes in some people they may overreact and the contractility can be reduced significantly. So if your ejection fraction, that's the number for your contractility, if it drops to less than 50 percent, then the FDA has put guardrails to make sure we recognize that, temporarily stop the drug, and resume. If your ejection fraction drops to less than 30 percent, then that's a major warning signal that that drug should be permanently discontinued.

The other important thing to keep in mind is also this drug gets metabolized through the liver through something called a cytochrome enzyme system, and there could be some drug interactions that have to be taken into account. So because of that, and at least at the current time, an experienced provider prescribing the drug is the better part of VALOR. The drug is currently approved under what is called the REMS, risk evaluation and mitigation strategy, wherein if you prescribe the drug, the patient needs to agree to participate and come back for periodic echoes monthly for the first three months and then three monthly thereafter. So this involves some logistics and detail understanding, which is why it is important that experienced providers prescribe this medication.

Steven Nissen:

So for patients that are interested, you run a Hypertrophic Cardiomyopathy Center and you could see new patients and you can counsel them about whether they're a candidate for the drug, do the evaluation. So I think it's probably important for everybody to know that we are here to help. You've got a great team behind you and for the patients, if you have this disease, hypertrophic cardiomyopathy, we'd be happy to help you.

Milind Desai:

Absolutely. Yes, at Cleveland Clinic we have the full spectrum of comprehensive services that we offer to our HCM patients. We have clinical doctors, we have a multiple nurse practitioners who are experienced in this. In fact, we now have an HCM nurse coordinator who helps navigate these patients as well as deal with the logistics of the Mavacamten prescription plus everything else. Surgeons, obviously we have world class interventional cardiologists, and all this is backed up by an absolutely stellar imaging team to make the diagnosis as well as ascertain prognosis and risk stratification.

Another important thing we have initiated in the last few months is as follows. Thanks to some generous support by our philanthropic donors, we have initiated a very ambitious genetic testing program, which basically you can choose to participate in, sign informed consent, and we will do your advanced genetic analysis not only for you, but also potentially for your first degree relatives. And this is not just for HCM, but for many cardiovascular diseases that are genetically mediated. So all in all, we provide the full spectrum of very high quality care, seamless care at the Cleveland Clinic.

Steven Nissen:

Thank you, Dr. Desai. And for the patients, this is really a wonderful time where new therapies are being developed that can help people with this disease really for the first time do this, and in some cases avoid surgery. But in those that need surgery, surgery has become very safe.

Milind Desai:

Absolutely. So if there are any questions, just check out our HCM Center website, which has dedicated phone numbers, emails. There are many ways you can reach us. Thank you so much.

Steven Nissen:

And thank you.

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